The Food and Drug Administration (FDA) has granted accelerated approval to Blenrep (belantamab mafodotin-blmf; GlaxoSmithKline) for the treatment of adults with relapsed or refractory multiple myeloma who have received at least 4 prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor and an immunomodulatory agent.
Belantamab mafodotin-blmf is a humanized, afucosylated, IgG1 anti-B cell maturation antigen (BCMA) monoclonal antibody conjugated to the cytotoxic agent, monomethyl auristatin F (MMAF). Upon binding to BCMA, belantamab mafodotin-blmf is internalized followed by release of MMAF, which intracellularly disrupts the microtubule network leading to cell cycle arrest and apoptosis.
The approval was supported by data from the pivotal, multicenter, open-label phase 2 DREAMM-2 trial that assessed the efficacy and safety of belantamab mafodotin-blmf in 196 patients with relapsed or refractory multiple myeloma after 3 or more lines of therapy that included an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody.
Patients were randomized to receive belantamab mafodotin-blmf 2.5mg/kg (n=97) or 3.4mg/kg (n=99) via intravenous infusion once every 3 weeks until disease progression or unacceptable toxicity. The primary end point was the overall response rate (ORR), defined as the proportion of patients with a confirmed partial response or better.
Findings showed an ORR in the 2.5mg/kg cohort of 31% (n=30; 97.5% CI, 21-43); 2 patients had a stringent complete response, 1 patient had a complete response, 15 patients had very good partial response, and 12 had a partial response. The median time to first response was 1.4 months (95% CI, 1.0-1.6). The median duration of response (DoR) had not yet been reached at the 6-month analysis, but 73% of responders had a DoR ≥6 months.
Continued approval of Blenrep for the treatment of relapsed or refractory multiple myeloma may be contingent upon verification and description of clinical benefit in confirmatory trials.
With regard to safety, the most common adverse reactions were keratopathy, decreased visual acuity, nausea, blurred vision, pyrexia, infusion-related reactions, and fatigue. Treatment with Blenrep has been associated with ocular toxicity that may result in changes in vision, including severe vision loss and corneal ulcer; of the 218 patients in the pooled safety population, 77% experienced ocular adverse reactions. Due to this risk, the product is only available through a restricted program called the Blenrep REMS.
Blenrep will be supplied as a preservative-free lyophilized powder in 100mg single-dose vials. The product is expected to be available at the end of August 2020.
For more information visit gsk.com.
1. FDA approves GSK’s Blenrep (belantamab mafodotin-blmf) for the treatment of patients with relapsed or refractory multiple myeloma. https://us.gsk.com/en-us/media/press-releases/fda-approves-gsk-s-blenrep-belantamab-mafodotin-blmf-for-the-treatment-of-patients-with-relapsed-or-refractory-multiple-myeloma/. Accessed August 6, 2020.
2. Blenrep [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2020.